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At least 685 records · Page 38Linked to original sources
PubMed1999

The site of the anti-emetic action of tachykinin NK1 receptor antagonists may exist in the medullary area adjacent to the semicompact part of the nucleus ambiguus.

NK1 receptor antagonists have been shown to act centrally and to produce a broad-spectrum anti-emetic action. To determine precisely the site of this action, we microinjected GR205171, an NK1 receptor antagonist, into the left medulla oblongata in decerebrate paralyzed dogs. The right medulla was transected 2.5 mm rostral to the obex to eliminate the emetic function of that half. Fictive retching induced by vagal stimulation was still observed after each of 32 injections (0.5-5 microgram in 1-30 microliter) in the area ventrolateral to the solitary complex in six dogs. Retching was also observed for 30 min or more after all but 2 of 30 injections (0.5-1 microgram in 0.5-1 microliter) in the area dorsal to the retrofacial nucleus in 17 dogs. In contrast, retching disappeared within 5-30 min after each of 20 injections (0.5-1 microgram in 1 microliter) in the area adjacent to the semicompact part of the nucleus ambiguus (scAMB) in 15 dogs. The threshold dose for abolition of the retching response was examined in seven dogs and was about 0.1 ng in 1 microliter. The maximum velocity of salivation occurred before the onset of retching and significantly decreased after its abolition. These results suggest that the site of the anti-emetic action of NK1 receptor antagonists may lie in a limited area adjacent to the scAMB, and that neurons in the site induce prodromal signs and retching in a sequential manner.

Animals↗
PubMed1997

Effects of ondansetron administration on opioid withdrawal syndrome observed in rats.

This study tested whether a 5-HT3 receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.

Animals↗
PubMed1997

Tolterodine--a new bladder-selective antimuscarinic agent.

Tolterodine is a new muscarinic receptor antagonist intended for the treatment of urinary urge incontinence and other symptoms related to an overactive bladder. The aim of the present study was to compare the antimuscarinic properties of tolterodine with those of oxybutynin, in vitro and in vivo. Tolterodine effectively inhibited carbachol-induced contractions of isolated strips of urinary bladder from guinea pigs (K(B) 3.0 nM; pA2 8.6; Schild slope 0.97) and humans (K(B) 4.0 nM; pA2 8.4; Schild slope 1.04) in a concentration-dependent, competitive manner. The affinity of tolterodine was similar to that derived for oxybutynin (K(B) 4.4 nM; pA2 8.5; Schild slope 0.89) in the guinea-pig bladder. Tolterodine (21-2103 nmol/kg (0.01-1 mg/kg); intravenous infusion) was significantly more potent in inhibiting acetylcholine-induced urinary bladder contraction than electrically-induced salivation in the anaesthetised cat. In contrast, oxybutynin displayed the opposite tissue selectivity. Radioligand binding data showed that tolterodine bound with high affinity to muscarinic receptors in urinary bladder (K(i) 2.7 nM), heart (K(i) 1.6 nM), cerebral cortex (K(i) 0.75 nM) and parotid gland (K(i) 4.8 nM) from guinea pigs and in urinary bladder from humans (K(i) 3.3 nM). Tolterodine and oxybutynin were equipotent, except in the parotid gland, where oxybutynin bound with 8-times higher affinity (K(i) 0.62 nM). Binding data on human muscarinic m1-m5 receptors expressed in Chinese hamster ovary cells showed that oxybutynin, in contrast to tolterodine, exhibits selectivity (10-fold) for muscarinic m3 over m2 receptors. The K(B) value determined for oxybutynin (4.4 nM) in functional studies on guinea-pig bladder correlated better with the binding affinity at muscarinic M2/m2 receptors (K(i) 2.8 and 6.7 nM) than at muscarinic M3/m3 receptors (K(i) 0.62 and 0.67 nM). The tissue selectivity demonstrated for tolterodine in vivo cannot be attributed to selectivity for a single muscarinic receptor subtype. However, the combined in vitro and in vivo data on tolterodine and oxybutynin may indicate either that muscarinic M3/m3 receptors in glands are more sensitive to blockade than those in bladder smooth muscle, or that muscarinic M2/m2 receptors contribute to bladder contraction.

Adult↗
PubMed1996

Changes in taste and satiety in dietary-restrained women following stress.

Stress has been shown to increase food consumption in women with high levels of dietary restraint (restrainers) but decrease consumption in nonrestrainers. The present study was designed to replicate the differential eating pattern following stress and measure physiological and subjective responses to food over repeated taste presentations. Restrained (N = 16) and nonrestrained (N = 16) women were given eight taste presentations of a food followed by an ad lib taste test. Between taste trials, half of the restrainers and nonrestrainers performed a variation of the Stroop stressor while remaining subjects sat quietly. Salivation to the food cue was measured at each trial as well as ratings of food liking, hunger, fullness, and arousal. Results showed significant effects of restraint on food liking and stress condition on hunger. Restrainers increased liking ratings over taste trials whereas ratings for nonrestrainers increased and then decreased to baseline levels by the last trial (p = 0.05). Nonstressed subjects showed an increase in hunger ratings, whereas ratings for stressed subjects did not show any stable directional pattern (p = 0.04). Salivary responses decreased for all groups (p = 0.01). A significant interaction of restraint by stress for intake was found (p = 0.03); restrainers increased consumption following stress whereas nonrestrainers decreased consumption as compared with controls. The data suggest that the Stroop task can influence intake in restrainers, but the changes in intake did not directly correspond to the changes observed during the presentations of the taste cues and stressor.

Adolescent↗
PubMed1997

The effect of dietary fat on salivary habituation and satiation.

This study was designed to explore the effect of dietary fat and carbohydrate on oral habituation. Forty women (18-21 years old) were randomized to 1 of 4 yogurt conditions that varied levels of dietary fat and carbohydrate. Subjects consumed 0.4 g of yogurt per pound per trial until they indicated fullness in up to 15 trials, with salivation, number of trials to fullness, and ratings of hedonics, appetite, and fullness measured. Subjects in the high-fat conditions demonstrated a significantly faster rate of salivary habituation than subjects in the low-fat conditions, and consumed less volume of yogurt but consumed more calories. The rate of habituation was not influenced by carbohydrate content of the yogurt. These findings suggest that oral habituation in humans is sensitive to macronutrient content of food.

Adolescent↗
PubMed2004

Anticipatory effects of food exposure in women diagnosed with bulimia nervosa.

OBJECTIVE: To investigate cephalic phase responses (CPRs) in women diagnosed with bulimia nervosa and to test the assumption that eating disordered individuals respond with more marked CPRs and higher increases in psychophysiological arousal to the presentation of food cues. METHOD: Thirteen female inpatients diagnosed with bulimia nervosa were compared to 15 non-eating disordered female volunteers. Participants were exposed to their preferred binge food in a single laboratory session with the possibility to eat immediately after the exposure trial. RESULTS: The results show greater salivation responses to food exposure and lower sympathetic arousal in patients diagnosed with bulimia nervosa than in non-eating-disordered participants. Distress and feelings of tension and insecurity during food exposure were higher in patients compared to controls. DISCUSSION: These results support the hypothesis that anticipatory cephalic phase responses are more marked in eating disordered individuals and may therefore play a role in the maintenance of binge eating behavior.

Adult↗
PubMed1999

The effect of pilocarpine and biperiden on salivary secretion during and after radiotherapy in head and neck cancer patients.

PURPOSE: The influence of parasympathicomimetic pilocarpine and anticholinergic biperiden on salivation in patients irradiated for malignant tumors of the head and neck region was assessed in a prospectively designed clinical study. METHODS AND MATERIALS: Sixty-nine patients, irradiated for head and neck cancer with salivary glands included in the irradiation fields, were randomly assigned into three groups (A, B, and C). Group A consisted of patients receiving pilocarpine, group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion, while group C comprised patients not receiving any xerostomy prevention therapy during or after radiotherapy. The quantity of secreted unstimulated saliva was measured before the beginning of radiotherapy, after 30 Gy of irradiation, on completed irradiation, and 3, 6, and 12 months after completion of radiotherapy. RESULTS: Saliva secretion has been found to be the least affected by irradiation treatment in the group of patients receiving biperiden throughout the course of radiotherapy. Six months after completed irradiation, the differences in the quantity of secreted saliva between groups C and B as well as between groups A and B were statistically significant (P = 0.002 and 0.05 respectively). In patients receiving pilocarpine during radiotherapy, and those in the control group, further decrease in saliva secretion was observed. One year after completed therapy, the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy: it amounted to 16% of the average quantity of saliva secreted before the beginning of irradiation. CONCLUSION: It seems that the inhibition of saliva production during irradiation treatment and the stimulation after completed radiotherapy may contribute to the preservation of salivary gland function after therapy.

Adult↗
PubMed1990

Autonomic indexes during the vestibular-visual conflict exposure: a squirrel monkey study.

To assess the dynamic changes of the autonomic neural responses evoked by vestibular-visual conflict (VVC) in the squirrel monkey, we analyzed the changes of salivary amount and sodium concentration, and the coefficient of variance (CV) of R-R intervals (RRI) along the time course of VVC exposure given in pitch plane. The sodium concentration and the amount of saliva showed clear increases at the first and second 15 min stimulation periods. The CV of RRI was found to increase over the entire periods of stimulation, and there was a significant difference between the rest value and those in stimulated periods. The correlation between the CV of RRI, and amount of salivation was highly positive. These results indicate the existence of a common pattern of autonomic neural response during VVC, and suggest usefulness of these indexes for objectively monitoring the severity of motion sickness.

Animals↗
PubMed1999

A pilot study of the disposition of pilocarpine in plasma, saliva and urine after a single oral dose.

Concentrations of pilocarpine in plasma, saliva and urine from three healthy male volunteers were measured using a fluorescence derivatisation method, following administration of a single 10 mg oral dose. Pharmacokinetic parameter values were estimated from concentration-time profiles. Linear correlations between plasma and saliva pilocarpine concentrations (r2=0.945, n=10, p<0.001; r2=0.954, n=12, p<0.001) and plasma concentrations and salivation rate (r2=0. 863, n=12, p<0.001; r2=0.862, n=15, p<0.001) were established. Pilocarpine and an unidentified metabolite, respectively 20.3% and 34.7% of the oral dose, were excreted into urine.

Adult↗
PubMed2003

The Pavlov Department of Physiology: a scientific history.

The scientific adventure of the Ivan Pavlov Department of Physiology is traced from Pavlov's and his students pioneer work on "psychic salivation" to the times of the Biological Station at Koltushi. The development of the Department after Pavlov's death is described and the research trends of the three present laboratories (Neurobiology of Integrative Brain Functions, Psychophysiology of Emotions, and Neurodynamic Correction of Psycho Neurological Pathology) are discussed.

Animals↗
PubMed2004

1. In vivo aroma release during eating of a model cheese: relationships with oral parameters.

This study aims to follow the kinetics of aroma compound release during model cheese consumption in order to clarify the relationships between flavor release and some oral parameters. Eight subjects participated in the study. Breathing, salivation, chewing, and swallowing were monitored during the eating process. Temporal nosespace analyses were performed using on-line atmospheric pressure ionization-mass spectrometry (API-MS) and off-line solid-phase Micro extraction-gas chromatography-mass spectrometry (SPME-GC-MS). Flavor release profiles were obtained only for ethyl hexanoate, heptan-2-one, and heptan-2-ol. Among them, only the concentrations of ethyl hexanoate and heptan-2-one could be determined by API-MS. Absence of competition between the aroma compounds was checked for both techniques. In-nose maximum concentration (C(max)) varied with aroma compounds. However, C(max) was reached at the same time (T(max)) for the three compounds. Interindividual differences were observed for most of the parameters studied and for all of the aroma compounds. They were related to the interindividual differences among the oral parameters. The aroma release parameters C(max) and AUC (area under the curve) could be related to respiratory and masticatory parameters. In most cases, the same relationships were observed whatever the nature of the aroma compound.

Cheese↗
PubMed2006

Release and perception of ethyl butanoate during and after consumption of whey protein gels: relation between textural and physiological parameters.

The influence of gel texture on parameters such as positioning of food material in the oral cavity during mastication, and salivation, and their influence on aroma release in vivo was studied. Retronasal perception was followed by means of time-resolved sensory evaluation, while volatile release patterns were observed by means of PTR-MS. A clear correlation was found between individual-specific consumption patterns and the respective sensory perception. Also, gel texture could be clearly correlated with respective physicochemical release patterns in vivo and to the corresponding retronasal aroma perception.

Adult↗
PubMed1992

Synthesis and substance P antagonist activity of naphthimidazolium derivatives.

The synthesis of unsymmetrical naphth[2,3-d]imidazolium and bridged naphth[2,3-d]imidazolium derivatives and their substance P (SP) antagonist activity are described. All compounds were evaluated for their ability to displace SP from neurokinin-1 (NK-1) receptor sites using standard receptor binding methodology (rat forebrain membrane). 1,3-Diethyl-2-[3-(1,3-dihydro-1,3,3-timethyl-2H-indol-2-ylidene) -1-propenyl]-1H-naphth[2,3-d]imidazolium chloride (7a), a representative compound in this series, was further evaluated for SP antagonist activity in a guinea pig ileum contractility assay. In vivo SP antagonist activity of 7a was demonstrated using SP-induced salivation and paw edema models performed in rats.

Animals↗
PubMed1992

The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst.

We describe the structure-activity relationship development of a series of quinuclidines which culminated in the first potent, selective, nonpeptide substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxy-phenyl)methyl]-1- azabicyclo[2.2.2]octan-3-amine, 3 (CP-96,345). Compound 3 is a potent displacer of [3H]SP binding in human IM-9 cells and blocks SP-induced and capsaicin-induced plasma extravasation, as well as SP-induced salivation in the rat in vivo. This compound may both help to further our understanding of the interactions of small molecules with peptide receptors and serve to evaluate the therapeutic potential of a SP antagonist.

Amino Acid Sequence↗
PubMed1990

Synthesis and biological evaluation of new antimuscarinic compounds with amidine basic centers. A useful bioisosteric replacement of classical cationic heads.

Amidines (guanidine, formamidine, and acetamidine) were introduced as substitutes for the cationic heads present in atropine, scopolamine, and corresponding quaternary derivatives. Amidine systems are intermediate in structure between tertiary amines and quaternary compounds, at least as regards ionization and electronic properties, but differ from the latter in shape (planar not tetrahedral). They have additional binding opportunities on account of their hydrogen-bond-forming capacity. The effect of the introduction of these cationic heads on the affinity for different muscarinic acetyl choline receptor (m-AcChR) subtypes was investigated in vitro, in binding displacement studies, and in functional tests on isolated organs. All new compounds (3a,b-5a,b) showed high affinity for the m-AcChR considered, comparable or slightly inferior to that of the parent drugs (1a-e). The new amidine derivatives proved effective as spasmolytic agents, with little tendency to cause central effects. However, no separation was achieved of spasmolytic and other untoward effects, like inhibition of salivation. Thus, amidine moieties are effective bioisosteric substitutes for conventional cationic heads present in antimuscarinic agents. Their unusual physical-chemical properties make them useful tools when modulation of pharmacokinetic or pharmacodynamic effects is required.

Amidines↗
PubMed1992

Pilocarpine disposition and salivary flow responses following intravenous administration to dogs.

Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates.

Animals↗
PubMed2004

Nizatidine and cisapride increase salivary secretion in rats.

Saliva is a neurally induced solution with buffering capacity against acidic solutions. Salivation therefore plays an important role in defending the esophageal mucosa against refluxed gastric acid and is evoked by cholinergic stimulation. Both nizatidine and cisapride are reported to increase acetylcholine concentrations in the postganglionic cholinergic synapses. We performed this study to clarify the effect of administration of nizatidine and cisapride on salivary secretion. Eight-week-old male Sprague-Dawley rats were used for the experiments. Histamine-stimulated gastric acid secretion was measured after intraduodenal administration of nizatidine or famotidine to determine the equipotent acid-suppressing doses. Salivary secretion was then measured for 3 hr after intraduodenal administration of nizatidine (30 mg/kg), famotidine (3 mg/kg), or cisapride (1 mg/kg). Both nizatidine and famotidine dose-dependently inhibited histamine-stimulated gastric acid secretion. Total salivary secretion was significantly increased by nizatidine (P = 0.02) and cisapride (P = 0.02) but not by famotidine (P = 0.50) compared with controls.

Animals↗
PubMed2003

Drug effects on salivary glands: dry mouth.

OBJECTIVE: To identify drugs associated with the complaint of dry mouth. MATERIALS AND METHODS: MEDLINE was searched for papers 1980-2002 using keywords, oral, mouth, salivary, drugs, dry mouth and xerostomia, and relevant secondary references were hand-searched. RESULTS: Evidence was forthcoming for a number of xerogenic drugs, especially antimuscarinic agents, some sympathomimetic agents, and agents affecting serotonin and noradrenaline uptake, as well as a miscellany of other drugs such as appetite suppressants, protease inhibitors and cytokines. CONCLUSION: Dry mouth has a variety of possible causes but drugs--especially those with anticholinergic activity against the M3 muscarinic receptor--are the most common cause of reduced salivation.

Cholinergic Antagonists↗